The role of vasopressin V1a receptor in diabetic nephropathy and the invention of new therapy.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: NONOGUCHI Hiroshi 兵庫医科大学, 医学部, 准教授 (30218341)
• Co-Investigator(Kenkyū-buntansha): NAKANISHI Takeshi 兵庫医科大学, 医学部, 教授 (70217769)
• Co-Investigator(Renkei-kenkyūsha): TOMITA Kimio 熊本大学, 大学院・生命科学研究部, 教授 (40114772) ; KAWAHARA Kastumasa 北里大学, 医学部, 教授 (70134525) ; NAKAYAMA Yushi 熊本大学, 大学院・生命科学研究部, 講師 (00363531)
• Project Period (FY): 2009 – 2011
• Keywords: 水・電解質代謝学 / 抗利尿ホルモン / レニン・アンジオテンシン・アルドステロン系 / ミネラルコルチコイド受容体 / 細胞質核内輸送

Research Abstract

We reported that vasopressin V1a receptor deficient mice show type 4 renal tubular acidosis, which is characterized by reduced renal function, metabolic acidosis and hyperkalemia. Since the colleting ducts are the main cite of acid secretion by the kidney, we established a new cell line of the intercalated cells(IN-IC cells) from SV40 large T antigen Tg rats. Using these cells, we also found that vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor by aldosterone in the intercalated cells. In conclusion, vasopressin V1a receptor is essential for acid-base regulation by aldosterone in intercalated cells. These data suggest the possibility of clinical use of vasopressin V1a receptor antagonist as an aldosterone antagonist.

Research Products

• [Journal Article] High Levels of Tumor Necrosis Factor-α Downregulate Antimicrobial Iron Transport Protein, Nramp1, in Chronic Hemodialysis Patients : A Key Factor for Infection Risk (2012)
  • Author(s): Moriguchi R, Otaki Y, Hazeki S, Shimada T, Matsumoto A, Kakita N, Kaibe S, Kuragano T, Nonoguchi H, Masayoshi N, Hasuike Y, Nakanishi T.
  • Journal Title: Am J Nephrol Volume: 35(4) Pages: 372-8
  • Peer Reviewed
• [Journal Article] The impact of ferritin fluctuations on stable hemoglobin levels in hemodialysis patients (2012)
  • Author(s): Yahiro M, Kuragano T, Kida A, Kitamura R, Furuta M, Hasuike Y, Otaki Y, Nonoguchi H, Nakanishi T.
  • Journal Title: Clin Exp Nephrol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Persistent homocysteine metabolism abnormality accelerates cardiovascular disease in hemodialyzed patients--the Nishinomiya Study (2012)
  • Author(s): Hasuike Y, Hama Y, Nonoguchi H, Hori K, Tokuyama M, Toyoda K, Hazeki S, Nanami M, Otaki Y, Kuragano T, Nakanishi T.
  • Journal Title: J Ren Nutr Volume: 22(1) Pages: 12-8
  • Peer Reviewed
• [Journal Article] Hepcidin : another culprit for complications in patients with chronic kidney disease (2011)
  • Author(s): Nakanishi T, Hasuike Y, Otaki Y, Kida A, Nonoguchi H, Kuragano T.
  • Journal Title: Nephrol Dial Transplant Volume: 26(10) Pages: 3092-100
  • Peer Reviewed
• [Journal Article] Toxicodynamic evaluation of a cisplatin-chondroitin sulfate complex using a perfused kidney and human proximal tubular cells (2011)
  • Author(s): Zhang JS, Kadowaki D, Nonoguchi H, Hirata S, Seo H, Imai T, Suenaga A, Giam Chuang VT, Otagiri M.
  • Journal Title: Ren Fail Volume: 33(6) Pages: 609-14
  • Peer Reviewed
• [Journal Article] Aldosterone requires vasopressin V1a receptors on intercalated cells to mediate acid-base homeostasis (2011)
  • Author(s): Izumi Y, Hori K, Nakayama Y, Kimura M, Hasuike Y, Nanami M, Kohda Y, Otaki Y, Kuragano T, Obinata M, Kawahara K, Tanoue A, Tomita K, Nakanishi T, NonoguchiH.
  • Journal Title: J Am Soc Nephrol Volume: 22(4) Pages: 673-80
  • DOI: Doi:10.168/ASN.2010050468
  • Peer Reviewed
• [Journal Article] Therapeutic efficacy of double filtration plasmapheresis in patients with anti-aquaporin-4 antibody-positive multiple sclerosis (2011)
  • Author(s): Munemoto M, Otaki Y, Kasama S, Nanami M, Tokuyama M, Yahiro M, Hasuike Y, Kuragano T, Yoshikawa H, Nonoguchi H, Nakanishi T.
  • Journal Title: J Clin Neurosci Volume: 18(4) Pages: 478-80
  • Peer Reviewed
• [Journal Article] Pathological role of aminolevulinate in uremic patients (2011)
  • Author(s): Hasuike Y, Nonoguchi H, Tokuyama M, Hata R, Kitamura R, Hori K, Nanami M, Otaki Y, Kuragano T, Nakanishi T.
  • Journal Title: Ther Apher Dial Volume: 15(1) Pages: 28-33
  • DOI: doi:10.1111/j.1744-9987.2010.00824.x.
  • Peer Reviewed
• [Journal Article] Importance of ferritin for optimizing anemia therapy in chronic kidney disease (2010)
  • Author(s): Nakanishi T, Kuragano T, Nanami M, Otaki Y, Nonoguchi H, Hasuike Y.
  • Journal Title: Am J Nephrol Volume: 32(5) Pages: 439-46
  • Peer Reviewed
• [Journal Article] Kidney function, proteinuria, and adverse outcomes (2010)
  • Author(s): Nonoguchi H, Nanami M, Nakanishi T.
  • Journal Title: JAMA Volume: 303(20) Pages: 2030
  • Peer Reviewed
• [Journal Article] Epoetins and mortality in patients with cancer (2009)
  • Author(s): Nonoguchi H, Otaki Y, Tokuyama M, Yamamoto S, Nakanishi T.
  • Journal Title: Lancet Volume: 374(9686) Pages: 287
  • Peer Reviewed
• [Journal Article] Low pH stimulates vasopressin V2 receptor promoter activity and enhances downregulation induced by V1a receptorstimulation (2009)
  • Author(s): Memetimin H, Izumi Y, Nakayama Y, Kohda Y, Inoue H, Nonoguchi H, Tomita K.
  • Journal Title: Am J Physiol Renal Physiol Volume: 297(3) Pages: 620-8
  • Peer Reviewed
• [Journal Article] Enhanced kidney, gallbladder and colon on delayed CT (2009)
  • Author(s): Munemoto M, Kawai K, Yamamoto S, Nonoguchi H, Nakanishi T.
  • Journal Title: Nephrology(Carlton) Volume: 14(3) Pages: 360
  • Peer Reviewed
• [Journal Article] Vasopressin and hyperosmolality regulate NKCC1 expression in rat OMCD (2009)
  • Author(s): Wakamatsu S, Nonoguchi H, Ikebe M, Machida K, Izumi Y, Memetimin H, Nakayama Y, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res Volume: 32(6) Pages: 481-7
  • Peer Reviewed
• [Journal Article] Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts (2009)
  • Author(s): Mouri T, Inoue T, Nonoguchi H, Nakayama Y, Miyazaki H, Matsuzaki T, Saito H, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res Volume: 32(5) Pages: 358-63
  • Peer Reviewed
• [Presentation] 間在細胞におけるバゾプレッシンV1a受容体によるミネラルコルチコイド受容体核内輸送制御機構 (2012)
  • Author(s): 野々口博史、永井孝憲、堀加穂理、泉裕一郎、蓮池由起子、田上昭人、中山裕史、河原克雅、冨田公夫、中西健
  • Organizer: 第89回日本生理学会シンポジウム
  • Place of Presentation: 松本
  • Year and Date: 2012-03-30
• [Presentation] Vasopressin V1a Receptor is required for Nucleocytoplasmic Transport of Minerelocorticid Receptor (2011)
  • Author(s): Nagai T, Hori K, Izumi Y, Hasuike Y, Nakayama Y, Nanami M, Otaki Y, Tomita K, Kawahara K, TanoueA, Nakanishi T, Nonoguchi H.
  • Organizer: 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111108-13
• [Presentation] Acid decreased the expression of Ca-sensing receptor in type-B of mouse kidney collecting duct intercalated cells (2011)
  • Author(s): Ysuoka Y, Sato Y, Izumi Y, Nonoguchi H, Kawahara K
  • Organizer: 44th Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111108-13
• [Presentation] アルドステロンとバゾプレッシンの相互作用におけるバソプレシンV1a受容体の役割 (2011)
  • Author(s): 堀加穂理、永井孝憲、泉裕一郎、蓮池由紀子、小瀧慶長、倉賀野隆裕、田上昭人、河原克雅、冨田公男、中西健、野々口博史
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20110615-17
• [Presentation] Mechanisms of Type 4(hyperkalemic) Renal Tubular Acidosis (2010)
  • Author(s): Hori K, Nagai T, Izumi Y, Nakayama Y, Hasuike Y, Nanami M, Yasuoka Y, Otaki Y, Tanoue A, Kawahara K, Tomita K, Nakanishi T, Nonoguchi H.
  • Organizer: 43rd Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Denver, USA
  • Year and Date: 20101116-21
• [Presentation] Dislocation of Mouse Collecting Duct Aquaporin-2 by Metabolic Acidosis : Role of Vasopressin V1a Receptor (2010)
  • Author(s): Yasuoka Y, Kobayashi M, Sato Y, Nonoguchi H, Tanoue A, Kawahara K
  • Organizer: 43rd Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Denver, USA
  • Year and Date: 20101116-21
• [Presentation] アルドステロンによる酸・塩基平衡においてバソプレシンV1a受容体は必須である (2010)
  • Author(s): 堀加穂理、永井孝憲、泉裕一郎、蓮池由紀子、小瀧慶長、倉賀野隆裕、田上昭人、河原克雅、冨田公男、中西健、野々口博史
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 20100616-18
• [Presentation] 水チャネルAQP2の腎集合管細胞内局在におけるアシドーシスの影響とバソプレシンV1aRの役割 (2010)
  • Author(s): 安岡有紀子、野々口博史、河原克雅
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 20100616-18
• [Presentation] Vasopressin V1a receptor deficient causes type 4 renal tubular acidosis (2009)
  • Author(s): Izumi Y, Nakayama Y, Memetimin H, Inoue H, Kohda Y, Tomita K, Tanoue A, Nonoguchi H.
  • Organizer: 42nd Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20091027-1101
• [Presentation] Regulation of aldosterone action by vasopressin V1a receptor in the intercalated cell (2009)
  • Author(s): Hori K, Kimura M, Izumi Y, Nakayama Y, Memetimin H, Kida A, Hasuike Y, Otaki Y, Tomita K, Tanoue A, Nakanishi T, Nonoguchi H
  • Organizer: 42nd Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 20091027-1101